Nervous tissue stimulation device and method

ABSTRACT

A method using a precisely controlled, computer programmable stimulus for neuroselective tissue stimulation that does not leave a sufficient voltage or electrical artifact on the tissue being stimulated that would interfere or prevent a monitoring system from recording the physiological response is utilized to evaluate the physiological conduction of the tissue being studied. A computer controls both the waveform, duration and intensity of the stimulus. An output trigger to the nerve response recording component controls the timing of its operation. A neuroselective nervous tissue response latency and amplitude may be determined. The computer controlled stimulus may also be administered for therapeutic purposes.

[0001] The present invention claims the benefits of the followingprovisional application for patent filed at the U.S. Patent andTrademark Office:

[0002] Ser. No. 60205073, May 18, 2000

FIELD OF THE INVENTION

[0003] This invention relates to a method and apparatus forneuroselective nerve conduction stimulation which permits neuroselectivenerve response monitoring which enhances the utility of the diagnosticor therapeutic procedure which pertains to the neurological condition ofan individual an animal or isolated nervous tissue being evaluated.Nervous tissue includes nerves and is defined for the purposes of thisspecification as any living tissue with electro-responsivecharacteristics. This would include tissues such as muscle tissue whichis electronically reactive.

BACKGROUND OF THE INVENTION

[0004] The measurement of the function of nerves and nervous tissue byassessing their ability to transmit impulses provides valuablediagnostic information for the practice of medicine, surgery,chiropractic and other health fields and biological research. Metabolic,toxic, compressive and other types of nerve damage, the effects ofinterventions including pharmaceuticals and also nerve regeneration maybe assessed using this information.

[0005] The nerve conduction velocity and amplitude evaluationtraditionally utilizes electronic or electromagnetic stimulation ofnervous tissue or nerve fibers to evoke a physiological response whichis conducted along the length of the nervous tissue. This physiologicalresponse is recorded at a distant site on the nerve or the tissueinnervated by this nerve such as muscle tissue. The nervous tissueresponse to this stimulus is recorded using an extremely sensitiveelectromagnetic amplifier. The distance between the site of stimulationand response recording is divided by the latency of the amplifiedrecorded response time from the time of the stimulus to determine theNerve Conduction Velocity (NCV) of this segment of the nerve. Theamplitude of the recorded signal provides information regarding theactual number of nerve fibers responding. Peripheral nerves are composedof individual nerve fibers if varying diameters.

[0006] There are three major subpopulations of peripheral nerve fibersbased on characterization of their fiber diameter. Any one of thesesubpopulations may become effected in a disease condition. Assessing theintegrity of all three sub- populations or selectively stimulating these3 populations of sensory nerve fibers is important for medicaldiagnostics, therapeutics and research purposes.

[0007] The nerves diameter also associated to its function. The largestdiameter sensory nerve fibers are associated with sensation such astouch whereas the smaller diameter fibers are associated with pressure,temperature and pain sensations. The typical peripheral nerve iscomposed of large, middle and small diameter fibers that comprise<10%,<10% and>80% of the total number of fibers respectively. The larger thediameter of the nerve fiber, the greater its responsiveness to anelectrical stimulus. The larger diameter nerve fibers have the fastestconduction velocity, the lowest electrical charge threshold and theshortest duration response signal (referred to as an Action Potential).A typical large diameter fiber has a conduction velocity of 50 m/swhereas a typical small diameter fiber has a conduction velocity of 1m/s. The larger diameter fibers have greater numbers of ion channels percross sectional surface area of exposed fiber in contrast with thesmaller diameter nerve fibers which have the lowest number of ionchannels per cross sectional surface area of exposed fiber. Thisdifference in the cross sectional number of ion channels may contributeto the largest diameter fibers also having the briefest inter-responserest or refractory period of<0.4 msec in comparison to up to 20 msec inthe smallest diameter fibers.

[0008] Presently existing technology for NCV evaluations utilizes asuprathreshold pulsed waveform of electrical or electromagnetic stimulusto evoke a nervous tissue response. A limitation of the presentlyexisting technology is that it stimulates all of the nerve fibers in theperipheral nerve simultaneously.

[0009] Although the larger diameter nerve fiber comprises less than 10%of the typical peripheral sensory nerve's fibers, they make up>90% ofthe volume of the nerve. As a consequence of the large fibers comprisingthe bulk of the volume of the nerve, they contribute over>90% of thenerves response electrical potential from the combined Action Potentials(referred to as the Compound Action Potential, CAP) from all of thevarious diameter nerve fibers. The major contribution to electricalpotential the CAP from the large diameter fibers drowns out the ActionPotential signals from the smaller diameter fibers. As a result, theconventional NCV evaluation is limited in that it is primarily onlycapable of evaluating the function of the large diameter nerve fibersand at the same time because it stimulates all of the fibers in thenerve it is painful. Any medical test or procedure that is painful haspoor patient compliance for initial and follow-up evaluations.

[0010] It is an aspect of the present invention to provide an electricalor electro- magnetic stimulus that permits neuroselective NCV andamplitude measures to be obtained from the three major sub-populationsof nerve fibers which will be much less painful and in-part painless incontrast with currently existing technology and result in superiorpatient compliance for evaluations than is possible using presentlyexisting NCV technology.

[0011] It is also an aspect of the present invention to improve thetherapeutic efficacy of interventions requiring precise nervestimulation with or without nerve response monitoring equipment.

[0012] A pulsed waveform may be mathematically described by FourierAnalysis in terms of its harmonic components. These components may bedescribed as related amplitude sine waves of specific harmonicfrequencies. Previous research has demonstrated neuroselectivity of anelectrical stimulus when it is administered in its harmonic componentsas a sinusoidal waveform as described in the following references:

[0013] 1) Katims, J.J., Long, D.M., Ng, L.K.Y. Transcutaneous NerveStimulation (TNS): Frequency and Waveform Specificity in Humans. AppliedNeurophysiology, Volume 49:86-91, 1986.

[0014] 2) Katims, J.J. Electrodiagnostic Functional Sensory Evaluationof the Patient with Pain: A Review of the Neuroselective CurrentPerception Threshold (CPT) and Pain Tolerance Threshold (PTT). PainDigest Volume 8(5), 219-230, 1998.

[0015] It is believed that the slow rate of depolarization of a lowfrequency (eg. 5 Hz) sinusoid stimulus permits the large diameter nervefibers, due to their fast responsiveness, to repolarize faster than thethis slow stimulus can polarize them. Therefore the low frequency sinewave stimulus is not sufficient to bring the large diameter nerve fibersto their threshold potential. The large diameter fibers have arefractory period as brief as 0.4 msec and a small diameter fiber canhave a refractory period as long as 20 msec. A period of 180° of a 2000Hz sinewave is 0.25 msec and a 180° period of a 5 Hz sinewave is 100msec in duration. This is illustrated in FIG. 10. The low frequencysinewave is of sufficient charge and duration to depolarize the smalldiameter nerve fibers to their threshold potential which enables them togenerate action potentials in response to this stimulus. This lowfrequency sinusoid waveform stimulus has such a slow rate ofdepolarization that the large diameter rapidly responding nerve fiberscan repolarize faster than this stimulus can depolarize it. In contrast,a 2000 Hz sinewave is too fast and has a relatively lower charge thanthe 5 Hz sinewave (approximately 400×less charge per 180° of stimulus).The differences between these two different frequency sinusoid waveformsis illustrated in FIG. 10.

[0016] Nervous tissue stimulation technology currently commerciallyavailable that is used for purposes of obtaining NCV measurementsutilizes a square or pulsed waveform stimulus which, in contrast to asinusoid or slowly rising waveform, has an almost instantaneous changein polarization. The most widely used methodology for conducting NCVstudies routinely administers the stimulation at 150% of the intensityrequired to evoke a maximal response as observed using a responsemonitoring apparatus. This intensity this 150% supramaximal responsestimulation causes a rapid change in the nerve tissue polarization andexcites all the subpopulations of nerve fibers at the same time andtherefore lacks the neuroselectivity of the sinusoid waveform ofspecific frequencies.

[0017] My previous patents, No. 4,503,863, No. 4,305,102, and No.5,806,522 describe a “Method and Apparatus for Transcutaneous ElectricalStimulation” using a continuous (i.e. of a duration over 0.5 seconds,much greater than 360° of a sinusoidal waveform constant alternatingcurrent stimulus of various frequencies for purposes including thedetermination of the neuroselective Current Perception Threshold (CPT)measurements using a non-invasive, non-aversive electrical stimulusapplied at various frequencies. Work has continued in this directionendeavoring to develop this technology to construct a neuroselectivenerve conduction velocity device. The technology described in theseabove cited CPT related patents was not compatible with currentlyexisting commercially available EMG devices. The problem was that afteradministering an alternating current stimulus to the skin forapproximately 0.5 seconds or more and then turning off the stimulus topermit recording of the nerves response, a voltage potential remained inthe subjects body and drowned out the possibility of recording any nerveresponse from the response monitoring electrode. The reason for thisvoltage potential remaining on the subject is that there are inductivereactance properties of human skin which result in the applied voltageand current going out of phase.

[0018] It was necessary in the development that ensued leading up to thepresent invention to develop entirely new type electrodiagnosticapparatus for neuroselective of nerve stimulation. Examples of prior artnerve conduction electrical or electromagnetic response stimulatorpatents include the following are set out below: Inventor(s) U.S. Pat.Nos. U.S. Patents Issue Date 4,807,643 Rosier  2/28/89 5,066,272 Eaton,et al. 11/19/91 5,143,081 Young, et al.  9/01/92 5,806,522 Katims 9/15/98 5,976,094 Gozani 11/02/99

SUMMARY OF THE INVENTION

[0019] It is an object of the present invention to overcome thedeficiencies in the prior art.

[0020] It is another object of the present invention be able to providea computer controlled electrical or electromagnetic stimulus signal thatmay be utilized to neuroselectively excite nerve fibers to generateresponses that may be recorded by a nerve response recording component.The ability to record these responses permits the neuroselectivedeterminations of the latency and amplitude of the nervous tissueresponse to the stimulus.

[0021] It is also an object of the present invention to employprogrammable circuitry to generate the output wave form signal used tostimulate the nervous tissue. It is also an object of the presentinvention to employ programmable circuitry to generate the outputwaveform signal used to stimulate the nervous tissue to be a 180° or a360° sinusoid waveform stimulus. The present invention when utilizing alow frequency sinusoid waveform stimulus (eg., 5 Hz), operates optimallyusing a 360° sinusoid waveform stimulus as opposed to the 180° stimulus.The 360° stimulus has a relative positive and negative component thattend to cancel each other during monitoring by a physiological responsemonitoring system. The 5 Hz 180° sinusoid waveform has only a positiveor a negative component alone. The 180° sinusoid waveform stimulus hassufficient unbalanced charge (positive or negative) effecting theresponse monitoring system to interfere with the actual monitoring ofthe physiological response. In contrast the 2000 Hz 180° sinusoidwaveform stimulus does not produce sufficient charge to interfere withthe functioning of standard physiological or nerve response monitoringsystems.

[0022] It is also an object of the present invention to provide aneuroselective nervous tissue stimulator apparatus that may be usedwithout leaving a voltage or electrical artifact on the tissue beingstimulated that would interfere or prevent a monitoring system fromrecording the neurophysiological response.

[0023] It is also an object of the present invention to employprogrammable circuitry to generate the output wave form stimulus used tostimulate the nervous tissue with rapidly increasing intensities andtherefore rapidly depolarize the nervous tissue. This rapidlydepolarizing stimulus permits the preferential stimulation of largerdiameter nerve fibers or more responsive nervous tissue. Examples ofsuch wave forms include a 1000 or 2000 Hz sinusoid or triangular shapes(monophasic or bi-phasic).

[0024] It is also an object of the present invention to employprogrammable circuitry to generate the output wave form stimulus used tostimulate the nervous tissue with slowly increasing intensities andtherefore slowly depolarizing the nervous tissue. This slowlydepolarizing stimulus permits the preferential stimulation of smallerdiameter nerve fibers of less reactive nerve tissue. Examples of suchwave forms include a 5 Hz sinusoid, triangular or elliptical shapes. Itis also an object of the present invention to provide an output signalthat may be repeatedly administered to permit a response monitoringsystem to conduct a signal averaging analysis.

[0025] It is also an object of the present invention to provide aneuroselective nervous tissue stimulator that may be used in conjunctionwith currently commercially available NCV, nervous tissue stimulator orthe Current Perception Threshold (CPT) apparatus described in Katims U.S. Pat. No. 5,806,522.

[0026] It is also an object of the present invention to provide aneuroselective nervous tissue stimulator apparatus that may be used withthe response recording component of currently commercially availableNerve Conduction Velocity (NCV) devices or may be included as acomponent of an NCV device with a response recording component.

[0027] It is also an object of the present invention to permit lesspainful motor and sensory NCV evaluations than are currently availablyusing the prior art technology. This feature enhances patient compliancefor initial and follow-up evaluations.

[0028] It is also an object of the present invention to provide aneuroselective nervous tissue stimulator apparatus that may becontrolled and monitored by an external computer.

[0029] It is also an object of the present invention to disclose amethod and apparatus for electrical or electromagnetic nerve stimulationthat is battery or line powered.

[0030] It is also an object of the present invention to disclose amethod and apparatus for electrical or electromagnetic nerve stimulationthat is capable of having its output waveform programed by use of acomputer.

[0031] It is also an object of the present invention to permit discretenervous tissue stimulation that does not interfere with nervous tissueresponse monitoring equipment where nervous tissue responses may berequired for monitoring therapeutic interventions, or monitoring in situof nerve responses for evaluating the response to a therapeuticintervention, for example blood concentrations of lidocaine or glucose.

[0032] It is also an object of the present invention to utilize thestimulus output for therapeutic purposes including nervous tissuestimulation that does not interfere with nervous tissue responsemonitoring equipment for pain relief including spinal cord stimulation,prosthetic nerve stimulation, therapeutic nervous tissue stimulationincluding the purposes of augmenting or attenuating normal or impairednerve function.

[0033] It is also an object of the present invention to disclose amethod and apparatus.

[0034] These advantages of the present system are critical and ofimportance, not only to the examination and to the examiner, but also tothe patient, and the utility of nerve conduction stimulation will beenhanced over currently existing technology. In summary, the apparatusof the present invention enables neuroselective nerve stimulation thatis not associated with a voltage charge remaining on the nervous tissue,or disrupting the physiological response monitoring system after thestimulus is turned off, that may be used for determinations of nerveconduction velocities and amplitudes that is impossible with the priorart devices. The greater amount of diagnostic information that isinherent in the present invention in the apparatus and in the method isa critical advantage to the great benefit of the patient and to thepublic being tested. Additionally the apparatus of the present inventionmay be used for therapeutic purposes.

BRIEF DESCRIPTION OF THE DRAWINGS

[0035]FIG. 1 is a block diagram illustration of the overall system;

[0036]FIG. 2 is a schematic diagram of the power supply used in thesystem;

[0037]FIG. 3 is a schematic diagram of the micro-controller section usedin the system;

[0038]FIG. 4 is a schematic diagram of the waveform synthesizer used inthe system;

[0039]FIG. 5 is a schematic diagram of the 360-degree waveformsynthesizer used in the system;

[0040]FIG. 6 is a schematic diagram of the MOSFET Output Stage used inthe system;

[0041]FIG. 7 is a schematic diagram of the Battery Integrator Schematicused in the system;

[0042]FIG. 8 is a schematic diagram of the battery charger circuit usedin the system;

[0043]FIG. 9 is an illustration of the back panel of the device used inthe system;

[0044]FIG. 10 Upper panel: Graph depicting 2 kHz and 5 Hz sinusoidalwaveforms drawn to scale. Lower panel: Graph of amplitude vs time forthe 2000 Hz and 5 Hz frequencies, depicting sinusoidal waveform;

[0045]FIG. 11 is an illustration of the system of the present inventionwith stimulating electrodes placed over the subjects wrist crease, witha technician operating the device. The device is also connected to anerve response monitoring system which is also connected to electrodesplaced on the index finger of the patient;

[0046]FIG. 12 is an illustration of the overall apparatus as it wouldappear when incorporated into a Current Perception Threshold (CPT)device.

[0047] Method Description

Device Operation

[0048] The apparatus of the present invention, being computercontrolled, is capable of functioning in various output modes determinedby the operator of the device through pressing switches on the controlpanel of the device related to mode selection. The mode selection of thepresent invention is for neuroselective conduction velocity andamplitude. This mode generates a 360° sinusoid at 3 differentfrequencies 2000 Hz, 250 Hz and 5 Hz. The example of the presentinvention includes an external nerve response monitoring system 34. Thisexample also illustrates the present invention incorporated into a CPTdevice, FIG. 12. An example of this neuroselective conduction velocityand amplitude modes of operation follows:

Initial start-up mode

[0049] After the technician 107 FIG. 11 presses the power button 225FIG. 12 and turns on the device 9, the liquid crystal display 100identifies the manufacturer of the device and any related informationregarding identification of the device.

[0050] The text in the display 100 FIG. 12 under device control changesto guide the operator as to the various steps in using the stimulatorincluding an electrode cable test.

[0051] The apparatus 9 FIG. 11 has its external trigger controlconnected to trigger input the external nerve response monitoring system34. This external nerve response monitoring system 34 can be anypresently commercially available nerve conduction device presentlyavailable with a functioning response monitoring system and externaltrigger control. An example would be a standard nerve conductionvelocity device or an EMG machine or an EEG machine or FMRI, PET orthermography imaging devices or other types of biological responsemonitor.

[0052] The device 9 electrodes 19 FIG. 12 are placed in the example inthe illustration over the median nerve proximal to the wrist crease ofthe subject 218 FIG. 11 being tested. Monitoring electrodes from theexternal nerve response monitoring system 34 are placed on the distalphalange of the index finger of the subject 218. The technician 107adjusts the intensity of the stimulus using intensity knob 20 FIG. 12according to the criteria that is selected for the test, for example,the intensity may be set to the patients Current Perception Threshold(CPT) intensity (as described in U. S. Pat. No. 5,806,522) or some othervalue such as the maximum intensity evoked response as observed from thenerve response monitoring system 34 FIG. 1.

[0053] The external trigger output of the device signals the nerveresponse monitoring to monitor the response of the nerves being studied.In this example the monitored response signal will permit the conductionvelocity and amplitude to be determined at the site of the monitoringelectrodes of the right index finger subject 218 FIG. 1. Mostcommercially available NCV machines also permit signal averaging. Thenerve responses evoked by the output signal of the present invention maybe repeatedly studied by signal averaging techniques to obtain anaveraged signal response if desired.

[0054] By using only a 360° sine wave signal there is not sufficientvoltage remaining on the subject to interfere with any monitoredresponse. This waveform overcomes the limitations imposed by thecontinuous sinewave stimulation and the lack of neuroselectivity of apulse or square waveform stimulus and permits neuroselective nerveconduction responses to be studied using nerve response monitoringsystems.

Apparatus Description

[0055] Referring to FIG. 1, the apparatus consists of the main board102, the user interface 10, Liquid Crystal Display 100, the charger 103which is a commercially available stand alone unit (e.g. Tamara, Inc.,Japan). There is also a charger section on the main board 102 shown inFIG. 8, for charging the battery 104. Alternatively a 6 volt powersource derived from a line source may be employed instead of a battery.

[0056] Referring to FIG. 1, the main board has a Power Supply Section(detailed in FIG. 2) that receives a 6-volt input from the battery 104.As a safety feature, the power supply FIG. 2 is inherently limitedthrough the use of small MOSFETS 238 and 239 (on Resistance of 0.3 Ohms)and a small transformer 210 (<5VA), thereby limiting the amount of poweravailable at to the output. This provides an ultimate back-up safetyfeature. Under the failure of any other portions of this circuitry,there is not sufficient high voltage power available to harm thepatient.

[0057] Power Supply Schematic FIG. 2 is a component of the main board102. The power supply section produces the necessary voltages using aswitching circuit with MOSFETS 238 and 239 to produce an AC input forthe primary of transformer 210. After rectification and filtering on thesecondary the following voltages are provided for the apparatus: VoltageReference # +150 200 +135 201 +120 202 −120 203 −135 204 −150 205 +14206 −14 207 +5 208 −5 209 (FIG. 4)

[0058] The power supply FIG. 2 also has an on/off function. The actualpower to the switching regulator FIG. 2 is passed through a relay 211.Relay 211 is controlled by an always-powered CMOS flip/flop 213. CMOSflip/flop 213 detects activation or depression of the power on button.

[0059] Referring to FIG. 2, the flip/flop 213 and associated logiccircuitry 214 monitors the status of the charging jack 215. If the extraset of contacts in the charging jack 215 are opened by insertion of aplug, then the logic circuitry 214 resets the flip/flop 213 which forcesthe relay 211 to open and turn off the entire unit. This sequence mayalso be actuated by the micro-controller 216 illustrated in FIG. 3, thisis the auto off function. The auto off function protects the batteryfrom accidental discharge.

[0060] Referring to FIG. 6, an additional safety feature is the use ofseparate relay 230 from the power supply relay 211 illustrated in FIG.2. The control signal for output signal relay 230 FIG. 6 is switched onapproximately one second after the power goes on. Relay 230 is switchedoff immediately when the on/off switch is pressed to turn the unit off,while the actual power for the unit goes off approximately one secondafter relay 230. Therefore, the output relay 230 is never closed whenthe power is turned on or turned off, thereby preventing accidentallydischarging the electrical stimulus to the subject while turning thedevice on or off. This design ensures there are no start-up transientsor turn-off transients. The output relay 230 FIG. 6 also interrupts theoutput ground. Therefore in the unlikely situation of the unit beinghooked up to a failed and shorted charger 103, while the charger isplugged into an incorrectly wired wall outlet. Where the live and groundare switched, and a subject is connected who is also touching a groundthere still will not be any hazard.

[0061] Referring to FIG. 2, the power supply is synchronized to the2-megahertz quartz crystal 212, which is also used for one of thewaveform generation systems as illustrated in FIG. 6. The frequenciesare generated by dividing the 2 megahertz crystal 212 until you generatefrequencies at 100 times the desired the output frequency. The 500 Hzsignal is generated to create the 5 Hz sinewave. Also generated is a 25kHz signal to generate the 250 Hz sinewave and a 200 kHz to generate the2 kHz sinewave. The 100×signal is used to clock a switched capacitorfilter 226 FIG. 4 and is then divided by 100 and provides an analoginput to the switched capacitor filter 226 FIG. 4. The switchedcapacitor filter 226 FIG. 4 extracts the fundamental frequency from thedivided signal. This feature produces a very clean sinewave, which uponinspection appears to have 100 timing steps. Since the same path isfollowed by all three frequencies, there are no amplitude variations.Additionally, since each frequency is traceable back to the quartzcrystal, the accuracy is that of the original crystal 212 shown in FIG.2.

[0062] The 360-degree sine wave is mathematically stored in 64 discretesteps in the PROM memory 219 FIG. 3. The micro-controller 216 retrievesthe data, then by adjusting the timing between applying the steps to themultiplying Digital/Analog (D/A) converter 234 FIG. 5 the length of thestimulus is adjusted. Operational amplifier 235 FIG. 5 converts theoutput current of 234 FIG. 5 to produce a voltage output. Potentiometer237 FIG. 5 adjusts the reference voltage, which adjusts the full-scaleoutput current of Digital/Analog (D/A) converter 234 FIG. 5 , thereforesetting the full-scale output voltage of amplifier 235 FIG. 5. Thefull-scale output adjustment allows the output to be adjusted to thesame output level of the switched capacitor filter 226 FIG. 4. Thereforeno intensity conversion is necessary when switching between continuousfull sinewave mode and 360 degree sine wave mode. The multiplexer 236FIG. 5 selects whether the output is in continuous full sine wave modeor 360 degree sinewave mode.

[0063] The duration of stimulus and timing of the presentation iscontrolled by a second crystal Y101 and the micro-controller 216 FIG. 3.The analog signal generated from the frequency synthesis section output240 of FIG. 4 or 241 FIG. 5 is multiplexed by 236 FIG. 5. The output 242FIG. 5 of the multiplexer 236 FIG. 5 is then applied to the input 243FIG. 4 of amplifier 244 FIG. 4. The output of amplifier 244 FIG. 4 isapplied to a multiplying Digital/Analog (D/A) converter 224 FIG. 4. Themultiplying D/A converter 224 is a 12-bit unit. Therefore, it has 4096individual steps. The device in the illustrated design uses the first4,000 of these steps. For this example only 210 discrete codes areavailable to the user. After multiplying through the D/A converter 224to set the selected amplitude, the sinewave produced is fed to atransconductance amplifier FIG. 6. The first section of thetransconductance stage 227 creates two half copies of the signal, one islevel shifted up to the high positive voltages and one is level shifteddown to the high negative voltages. Current mirrors 245 and 246 FIG. 6,whose gains are approximately 6.2 are used to produce output currentsfrom the two half signals, which are then combined at the output 229.The output current produced is a constant current regardless of thepatients skin impedance, except of course when clipping has beenindicated. The output signal then goes through an output relay 230 tothe output jack 253.

[0064] Referring to FIG. 1, the LCD display 100 is directly driven offone of the micro-controller 216 ports as shown in FIG. 3. Referring toFIG. 3, this connection is a standard seven-line interface 218. The unitalso provides an output for triggering other instruments 217 FIG. 3.

[0065] Referring to FIG. 7, the battery voltage monitoring function is amicro-controller 216 controlled dual slope integration technique usingcomparator 221 FIG. 7 and an operational amplifier 222 FIG. 7 to measurethe battery 104 FIG. 1 voltage. Comparator 220 FIG. 7 and comparator 252FIG. 7 provide clipping information. Comparator 223 FIG. 7 provides thebattery discharge function.

[0066] Referring to FIG. 8, the main board incorporates a batterycharger circuit. A bridge rectifier 231 FIG. 8 is provided on thecharger input. This allows the use of a charger with either centerpositive or center negative polarity. There is also a Polyfuse RTM.current limited device 232 FIG. 8 (manufactured by Raychem, USA), whichtakes the place of a fuse. The charger circuit FIG. 8 takes the rawunregulated voltage being provided by the charger unit 103 FIG. 1 andproduces a precisely regulated 7 volt level for the battery 104 withoutthe risk of overcharging, thereby significantly enhancing the life ofthe battery. The use of the bridge rectifier 231 FIG. 8 and internalregulator 247 FIG. 8 also allows a wide variety of chargers to be usedwith the unit. This simplifies the production of units for operationalcapability using the various types of voltages found in many parts ofthe world.

[0067] The of External Computer Control port 250 FIG. 9 is opticallyisolated. There is no Ohmic connection between the port and any subjectcircuitry. The External Computer control port 250 FIG. 9 is interfacedto the micro-controller 216 FIG. 3. This permits the attachment of anexternal computer 251 FIG. 1 to control or monitor the apparatus of thepresent invention/

[0068] This External Computer Control port 250 FIG. 9 utilizes a RS-232chip set, a transformer for power, and four optical-isolators for datatransfer all on separate circuit board for safety reasons. This designprovides in excess of 2,500 Volts isolation. Therefore in the unlikelyevent of a power supply failure of an attached computer device while thesubjects connected, safety is still maintained.

[0069] Alternatively the output of the device may be delivered aninductor to generate magnetic fields for electromagnetic stimulation.

[0070]FIG. 10 provides two illustrations of sine waveforms. The upperpanel is a graph of amplitude vs time for the 2000 Hz and 5 Hzfrequencies, depicting 2 kHz and 5 Hz waveforms drawn to scale. Thelower panel is a graph of amplitude vs time for the 2000 Hz and 5 Hzfrequencies, depicting both sinusoidal waveforms of the same intensityand this is not drawn according to scale.

[0071] The output stimulus of the present invention may also be utilizedfor analgesia evaluation, motor nerve block studies and other types ofnerve conduction studies including H wave and F wave and SomatosensoryEvoked Potential and EEG, EKG and other electrophysiological responserelated studies.

[0072] Although the present invention has been described in some detailby way of illustration and example for purposes of clarity andunderstanding, it will, of course, be understood that various changesand modifications may be made with the form, details, and arrangementsof the parts without departing from the scope of the invention as setforth in the following claims.

1. An apparatus with computer control used in neuroselectively evokingresponses from nervous tissue using electronic or electromagneticstimulation that does not leave a sufficient voltage or electricalartifact on the tissue being stimulated that would interfere or preventa monitoring system from recording the physiological response.
 2. Theapparatus in claim 1 may be recorded by a nerve response recordingcomponent including an output trigger to the nerve response recordingcomponent.
 3. An apparatus in claim 1 employs programmable circuitry togenerate the output wave form signal used to stimulate the nervoustissue.
 4. The apparatus in claim 1 employs programmable circuitry togenerate the output wave form signal used to stimulate the nervoustissue to be a 180° or a 360° sinusoid waveform stimulus.
 5. Theapparatus may be used in conjunction or as a component of currentlycommercially available NCV, nervous tissue monitor or the CurrentPerception Threshold (CPT) apparatus described in Katims U.S. Pat. No.5,806,522.
 6. The apparatus in claim 1 may be monitored, programed andcontrolled by an external computer.
 7. The apparatus of claim 1 usingquartz crystal timing.
 8. The apparatus of claim 1 generating a constantcurrent output.
 9. The apparatus of the present invention provides aneuroselective nervous tissue stimulator apparatus that may be used withthe response recording component of currently commercially available NCVdevices or may be included as a component of an NCV device with aresponse recording component.
 10. The apparatus in claim 1 may employprogrammable circuitry to generate the output waveform stimulus used tostimulate the nervous tissue with rapidly increasing intensities andtherefore rapidly depolarize the nervous tissue to permit thepreferential stimulation of larger diameter nerve fibers or moreresponsive nervous tissue.
 11. The apparatus in claim 1 may employprogrammable circuitry to generate the output wave form stimulus used tostimulate the nervous tissue with slowly increasing intensities andtherefore slowly depolarizing the nervous tissue. This slowlydepolarizing stimulus permits the preferential stimulation of smallerdiameter nerve fibers of less reactive nerve tissue. Examples of suchwave forms include a 5 Hz sinusoid, triangular or elliptical shapes. 12.The apparatus in claim 1 may provide an output signal that may berepeatedly administered to permit a response monitoring system toconduct a signal averaging analysis.
 13. The apparatus in claim 1 mayprovide an output signal that may be delivered an inductor to generatemagnetic fields for electromagnetic stimulation.
 14. The method of using180 or 360 degree sinewave electrical or electromagnetic stimulation ofvarious frequencies to obtain painless and neuroselective stimulation toevoke nervous tissue responses which may be monitored by responsemonitoring equipment to determine response latencies and amplitudes. 15.The method of using a slowly depolarizing stimulus waveform ofelectrical or electromagnetic stimulation to selectively evoke smallfiber or slowly responsive nervous tissue responses or a rapidlydepolarizing stimulus waveform of electrical or electromagneticstimulation to selectively evoke large fiber or rapidly responsivenervous tissue responses where the stimulus does not leave a voltagepotential on the tissue being stimulated that could interfere wit anervous tissue response monitoring system.
 16. The method of claims 8 or9 that may be applied to human, animal or isolated nervous tissue. 17.The method of using neuroselective stimulation in order to obtainrelatively painless nerve conduction velocity and amplitudemeasurements.
 18. The method of using neuroselective stimulation inorder to permit discrete nervous tissue stimulation that does notinterfere with nervous tissue response monitoring equipment wherenervous tissue responses may need to be monitored such as for monitoringtherapeutic interventions, including in situ monitoring of nerveresponses for evaluating the response to a therapeutic intervention, 19.The method of using discrete neuroselective stimulation for therapeuticpurposes including nervous tissue stimulation that does not interferewith nervous tissue response monitoring equipment for pain reliefincluding spinal cord stimulation, prosthetic nerve stimulation,therapeutic nervous tissue stimulation including the purposes ofaugmenting or attenuating normal or impaired nerve function.